The invention relates to a process for the monitoring of contaminant removal during the purification process of a pharmaceutical product produced by a host cell.
Monitoring the removal of contaminants during the purification process of a pharmaceutical product produced by a host cell is necessary to acquire market approval of the pharmaceutical product. For market approval of the pharmaceutical product, it must be shown that the purification process is reproducible and that the pharmaceutical product is produced with a constant quality (i.e. purity). Therefore, there is a need for reliable methods for monitoring contaminant removal during the purification process of a pharmaceutical product.
Detection methods used for the monitoring of contaminant removal during the purification process of a pharmaceutical product produced by a host cell are known in the art. The known methods make use of immunological methods, for example ELISA or Western blot mostly combined with other known methods not based on immunology, for example 1- and 2D-gelelectrophoresis or (reversed phase) HPLC.
A disadvantage of the known immunological methods is that the used antibodies are raised against certain proteins only. Typically, antibodies are only raised against immunogenic host cell proteins. Therefore, contaminants other than said immunogenic host cell proteins cannot be detected by immunological methods.
In immunological methods, polyclonal antibodies raised against (host cell) proteins in a host animal (e.g. rabbit, goat, mouse) are usually used. Therefore, immunological methods can only detect the (host cell) proteins that are capable of inducing an immunological response in the host animal. Typically, this accounts for the detection of only 20-30% of the total (host cell) proteins. As polyclonal antibodies are usually not raised in humans, the remaining non-detected host cell proteins may well cause an immunological reaction in humans. In addition, other contaminants besides (host cell) proteins are not detected either.
The disadvantage of both the immunological and the other known detection methods not based on immunological detection is that they do not have a high sensitivity combined with the ability to detect individual proteins; the known methods either detect individual proteins with a relatively low sensitivity (Western blot, HPLC, 1- and 2-D gelelectrophoresis) or detect a total protein signal with a higher sensitivity (e.g. ELISA).